Propionibacterium acnes (P. acnes) cause an inflammatory acne that plays an important role in the pathogenesis of acne by inducing inflammatory mediators. Bee venom therapy has been used in oriental medicine for the relief of pain and the treatment of inflammatory diseases. However, a direct effect of bee venom in skin inflammation has not been established. The purpose of this study was to investigate anti-inflammatory properties of bee venom in skin inflammation stimulated by heat-killed P. acnes using human keratinocytes and monocytes cell line. P. acnes stimulates the production of proinflammatory cytokines such as interleukins-1β, -8, interferon-γ and tumor necrosis factor-α in HaCaT and THP-1 cells. Bee venom effectively inhibits the secretion of IL-1β, IL-8, IFN-γ, and TNF-α. P. acnes treatment activates the expression of TLR2, which results in IL-8 expression. However, bee venom treatment reduces the expression of TLR2 and IL-8. Based on these results, bee venom has effects on anti-inflammatory activity against P. acnes in HaCaT and THP-1 cells.